Prenatal diagnosis and genetic counseling for two pedigrees with pericentric inversion of chromosome 18

Abstract

Objective To investigate the roles of ultrasound, laboratory methods, and genetic diagnostic techniques in screening and diagnosing fetuses with an unbalanced recombination of chromosome 18[rec(18)] due to parental pericentric inversion, and the relationship between rec(18) fetal phenotypes and their recombinant chromosomes. Methods We analyzed two pedigrees with pericentric inversion of chromosome 18 (including the fetuses and their parents) which received prenatal diagnosis and genetic counseling on March 2017 and March 2018 respectively at Xiamen Maternity and Children Health Care Hospital through karyotype analysis, chromosome microarray analysis(CMA) and fluorescence in situ hybridization (FISH). Literatures were retrieved from Scientific Citation Index, PubMed, China National Knowledge Infrastructure(CNKI) and Wanfang Data from 1970 to June 2018. The genetic counseling records, ultrasound and laboratory findings, pregnancy outcomes of families with pericentric inversion of chromosome 18 in this study and the included literatures were reported and analyzed. Results Non-invasive prenatal testing (NIPT) of one case indicated high risk of fetal trisomy 18 at 22 weeks of gestation. And the imaging examination indicated that fetus had interventricular septal defect and micrognathia at 24+2 weeks. Prenatal diagnosis confirmed that the fetal karyotype was 46,XY,rec(18)dup(18q)inv(18)(p11.32q12.1) pat, which was originated from his father whose karyotype was 46,XY,inv(18)(p11.32q12.1). In the other case, serum screening testing indicated high risk of fetal trisomy 18 at 12+3 weeks. Imaging examination indicated that fetus had thickened nuchal translucency at 13+3 weeks and bilateral choroid plexus cysts at 15+6 weeks. Prenatal diagnosis confirmed that the fetal karyotype was 46,XY,rec(18)dup(18q)inv(18)(p11.32q12.1) mat, which was originated from his mother whose karyotype was 46,XX,inv(18)(p11.32q12.1). Among the nine fetuses, including seven from five pedigrees reported in the literature retrieved and two from the two pedigrees we reported, seven showed abnormal soft markers or structures in ultrasound and three of the seven pedigrees had high risk of fetal trisomy 18. Conclusions Ultrasound screening is highly sensitive in detecting rec(18) fetuses, yet the association between ultrasound features and fetal karyotypes is not clear. The combination of multiple genetic analysis methods, including karyotype analysis, CMA and FISH, may be conducive to clarifying the types and sources of complex derived chromosomes. Key words: Chromosomes, human, pair 18; Chromosome inversion; Ultrasonography, prenatal; Genetic counseling